Germfree, colostrum-deprived piglets obtained by aseptic hysterectomy are immunologically "virgin" as indicated by the absence of immunoglobulin and "background" antibody-forming cells. They are, however, highly immunologically competent as demonstrated by excellent antibody response upon antigenic stimulation. There is evidence, therefore, that preexisting "natural" antibody is not required for antibody formation. "Background" hemolytic plaque-forming cells do not arise spontaneously without specific antigenic stimulation. These results support the concept that antibody formation is initiated only by specific antigenic stimulation. Histological, electron microscopic, immunohistological and radioimmunological techniques will be used to define the sites and nature of antigen-cell-cell interactions and proliferation and differentiation for the ontogeny of the immune response. The tissue culture method of Mishell and Dutton along with cell fractionation and reassociation and the effect of various antisera will be used to resolve the in vitro induction of the "true" primary immune response, the nature of cells and their interactions. Antigenic competition experiments in vivo and in vitro will test the potentiality of immunocompetent cells. A lymphocyte transformation assay for various mitogens, mixed lymphocyte culture reactions and cytotoxicity assays for allo and xenogeneic systems will also be used to investigate the cellular origin and induction of cellular immunity. Studies with this unique system will provide basic knowledge on the cellular and molecular basis of the initiation or induction of humoral and cellular immunity. This may lead to understanding the immune surveillance mechanism against malignancy or tumor immunity as well as transplantation immunity.